Ultrabroadband plasmon driving selective photoreforming of methanol under ambient conditions.

Liquid methanol has the potential to be the hydrogen energy carrier and storage medium for the future green economy. However, there are still many challenges before zero-emission, affordable molecular H2 can be extracted from methanol with high performance. Here, we present noble-metal-free Cu-WC/W plasmonic nanohybrids which exhibit unsurpassed solar H2 extraction efficiency from pure methanol of 2,176.7 µmol g-1 h-1 at room temperature and normal pressure. Macro-to-micro experiments and simulations unveil that local reaction microenvironments are generated by the coperturbation of WC/W's lattice strain and infrared-plasmonic electric field. It enables spontaneous but selective zero-emission reaction pathways. Such microenvironments are found to be highly cooperative with solar-broadband-plasmon-excited charge carriers flowing from Cu to WC surfaces for efficient stable CH3OH plasmonic reforming with C3-dominated liquid products and 100% selective gaseous H2. Such high efficiency, without any COx emission, can be sustained for over a thousand-hour operation without obvious degradation.

Glial, Neuronal, Vascular, Retinal Pigment Epithelium, and Inflammatory Cell Damage in a New Western Diet-Induced Primate Model of Diabetic Retinopathy.

This study investigated retinal changes in a Western diet (WD)-induced nonhuman primate model of type 2 diabetes. Rhesus nonhuman primates, aged 15 to 17 years, were fed a high-fat diet (n = 7) for >5 years reflective of the traditional WD. Age-matched controls (n = 6) were fed a standard laboratory primate diet. Retinal fundus photography, optical coherence tomography, autofluorescence imaging, and fluorescein angiography were performed before euthanasia. To assess diabetic retinopathy (DR), eyes were examined using trypsin digests, lipofuscin autofluorescence, and multimarker immunofluorescence on cross-sections and whole mounts. Retinal imaging showed venous engorgement and tortuosity, aneurysms, macular exudates, dot and blot hemorrhages, and a marked increase in fundus autofluorescence. Post-mortem changes included the following: decreased CD31 blood vessel density (P < 0.05); increased acellular capillaries (P < 0.05); increased density of ionized calcium-binding adaptor molecule expressing amoeboid microglia/macrophage; loss of regular distribution in stratum and spacing typical of ramified microglia; and increased immunoreactivity of aquaporin 4 and glial fibrillary acidic protein (P < 0.05). However, rhodopsin immunoreactivity (P < 0.05) in rods and neuronal nuclei antibody-positive neuronal density of 50% (P < 0.05) were decreased. This is the first report of a primate model of DR solely induced by a WD that replicates key features of human DR.

Learning from perpetrator replacement to remove crime opportunities and prevent poaching of the Sundarbans tiger.

Illegal wildlife trade (IWT) is one of the leading causes of the decline in high-value species. Crime-reduction strategies to counter IWT can have unintended effects, with crime displacement occurring when offenders react to such interventions. Despite the value of understanding how and why displacement occurs for informing conservation strategies, few examples are published. We explored a case of perpetrator replacement following an intervention and drew lessons for conservation strategies for high-value species. Poaching and subsequent trade threaten the Sundarbans tiger (Panthera tigris). Pirate gangs were the dominant poachers from 1980 to 2017, but following an extensive campaign, the Sundarbans was declared pirate free in 2018. We interviewed 280 individuals, including 100 tiger poachers, from 26 administrative unions bordering the Sundarbans and used interviewee responses to compare the poaching situation during and after the pirate era. We analyzed the spatial distribution of tiger poachers among the unions and used crime script analysis of the dominant poacher type to identify intervention. Because pirates opportunistically poached tigers, the government's successful counter-pirate campaign inadvertently removed the dominant tiger poaching type. However, a temporary reduction in poaching was rapidly cancelled out by the emergence of at least 32 specialist tiger-poaching teams. With the risk of extortion and robbery from pirates gone, other groups increased the frequency of opportunistic and targeted tiger poaching. Based on expert interviews, we estimated that 341 tiger poachers of all types are active throughout the unions, with 79% of specialists concentrated in 27% of unions. The highly focused counter-pirate campaign reduced motivations and opportunities for piracy but left intact the opportunity structure and trade connections for tiger poaching, and with insufficient enforcement officers trading has flourished. Interventions targeting opportunities for poaching by specialist tiger poachers include heightened surveillance and reporting mechanisms and alternative livelihood provision to disincentivize poaching.

Aprendizaje a partir de la sustitución del infractor para eliminar las oportunidades de crimen y prevenir la caza furtiva del tigre de Sundarbans Resumen El mercado ilegal de fauna (MIF) es una de las principales causas de la declinación de especies importantes. Las estrategias de reducción de crímenes para contrarrestar el MIF pueden tener efectos no deseados, como el desplazamiento del crimen que ocurre cuando los infractores reaccionan a dichas intervenciones. A pesar de lo valioso que es para las estrategias de conservación entender cómo y por qué ocurre este desplazamiento, se publican pocos ejemplos. Exploramos un caso de sustitución del infractor después de una intervención sacamos lecciones para las estrategias de conservación de especies importantes. La caza furtiva y el mercado subsecuente son una amenaza para el tigre de Sundarbans (Panthera tigris). Los piratas fueron los cazadores dominantes entre 1980 y 2017, pero después de una campaña exhaustiva, el Sundarbans fue declarado libre de piratas en 2018. Entrevistamos a 280 individuos, incluidos 100 cazadores furtivos, de 26 uniones administrativas que rodean al Sundarbans y usamos sus respuestas para comparar la situación de la caza furtiva durante y después de los piratas. Analizamos la distribución espacial de los cazadores furtivos entre las uniones y usamos el análisis de escritura criminal del tipo dominante de cazador para identificar las intervenciones. Ya que los piratas eran cazadores furtivos oportunistas, la campaña exitosa del gobierno para contrarrestarlos eliminó sin saberlo el tipo dominante de caza furtiva. Sin embargo, una reducción temporal de la caza se canceló rápidamente con la emergencia de al menos 32 equipos especialistas en la cacería furtiva de los tigres. Sin el riesgo de la extorsión o robo por parte de los piratas, otros grupos incrementaron la frecuencia de la cacería oportunista y focalizada. Con base en las entrevistas a expertos, estimamos que 341 cazadores de tigres de todos los tipos están activos en las uniones, con 79% de los especialistas concentrados en 27% de las uniones. La campaña focalizada anti-piratas redujo las motivaciones y oportunidades de piratería, pero no afectó la estructura de oportunidades y conexiones mercantiles de la cacería furtiva de tigres, lo cual, sumado a la falta de suficientes agentes policiales, ha aumentado el mercado. Las intervenciones enfocadas en las oportunidades de cacería de los cazadores especialistas incluyen una mayor vigilancia y mecanismos de reporte y el suministro de sustentos alternativos para desalentar la cacería furtiva.

Corticospinal and peripheral responses to heat-induced hypo-hydration: potential physiological mechanisms and implications for neuromuscular function.

Heat-induced hypo-hydration (hyperosmotic hypovolemia) can reduce prolonged skeletal muscle performance; however, the mechanisms are less well understood and the reported effects on all aspects of neuromuscular function and brief maximal contractions are inconsistent. Historically, a 4-6% reduction of body mass has not been considered to impair muscle function in humans, as determined by muscle torque, membrane excitability and peak power production. With the development of magnetic resonance imaging and neurophysiological techniques, such as electromyography, peripheral nerve, and transcranial magnetic stimulation (TMS), the integrity of the brain-to-muscle pathway can be further investigated. The findings of this review demonstrate that heat-induced hypo-hydration impairs neuromuscular function, particularly during repeated and sustained contractions. Additionally, the mechanisms are separate to those of hyperthermia-induced fatigue and are likely a result of modulations to corticospinal inhibition, increased fibre conduction velocity, pain perception and impaired contractile function. This review also sheds light on the view that hypo-hydration has 'no effect' on neuromuscular function during brief maximal voluntary contractions. It is hypothesised that irrespective of unchanged force, compensatory reductions in cortical inhibition are likely to occur, in the attempt of achieving adequate force production. Studies using single-pulse TMS have shown that hypo-hydration can reduce maximal isometric and eccentric force, despite a reduction in cortical inhibition, but the cause of this is currently unclear. Future work should investigate the intracortical inhibitory and excitatory pathways within the brain, to elucidate the role of the central nervous system in force output, following heat-induced hypo-hydration.

A Survey of Combat Athletes' Rapid Weight Loss Practices and Evaluation of the Relationship With Concussion Symptom Recall.

OBJECTIVE: There is a high incidence of concussion and frequent utilization of rapid weight loss (RWL) methods among combat sport athletes, yet the apparent similarity in symptoms experienced as a result of a concussion or RWL has not been investigated. This study surveyed combat sports athletes to investigate the differences in symptom onset and recovery between combat sports and evaluated the relationships between concussion and RWL symptoms. DESIGN: Cross-sectional study. SETTING: Data were collected through an online survey. PARTICIPANTS: One hundred thirty-two (115 male athletes and 17 female athletes) combat sport athletes. INTERVENTIONS: Modified Sport Concussion Assessment Tool (SCAT) symptom checklist and weight-cutting questionnaire. MAIN OUTCOME MEASURES: Survey items included combat sport discipline, weight loss, medical history, weight-cutting questionnaire, and concussion and weight-cutting symptom checklists. RESULTS: Strong associations ( rs = 0.6-0.7, P < 0.05) were observed between concussion and RWL symptoms. The most frequently reported symptom resolution times were 24 to 48 hours for a weight cut (WC; 59%) and 3 to 5 days for a concussion (43%), with 60% to 70% of athletes reporting a deterioration and lengthening of concussion symptoms when undergoing a WC. Most of the athletes (65%) also reported at least one WC in their career to " not go according to plan ," resulting in a lack of energy (83%) and strength/power (70%). CONCLUSIONS: Rapid weight loss and concussion symptoms are strongly associated, with most of the athletes reporting a deterioration of concussion symptoms during a WC. The results indicate that concussion symptoms should be monitored alongside hydration status to avoid any compound effects of prior RWL on the interpretation of concussion assessments and to avoid potential misdiagnoses among combat athletes.

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease.

Clearance of ocular fluid and metabolic waste is a critical function of the eye in health and disease. The eye has distinct fluid outflow pathways in both the anterior and posterior segments. Although the anterior outflow pathway is well characterized, little is known about posterior outflow routes. Recent studies suggest that lymphatic and glymphatic systems play an important role in the clearance of fluid and waste products from the posterior segment of the eye. The lymphatic system is a vascular network that runs parallel to the blood circulatory system. It plays an essential role in maintenance of fluid homeostasis and immune surveillance in the body. Recent studies have reported lymphatics in the cornea (under pathological conditions), ciliary body, choroid, and optic nerve meninges. The evidence of lymphatics in optic nerve meninges is, however, limited. An alternative lymphatic system termed the glymphatic system was recently discovered in the rodent eye and brain. This system is a glial cell-based perivascular network responsible for the clearance of interstitial fluid and metabolic waste. In this review, we will discuss our current knowledge of ocular lymphatic and glymphatic systems and their role in retinal degenerative diseases.

Aberrant expression of myeloid antigens in patients of acute lymphoblastic leukaemia.

OBJECTIVE: To determine the immunophenotypic pattern and aberrant expression of myeloid antigens in newly diagnosed patients of acute lymphoblastic leukaemia(ALL). METHODS: This descriptive cross-sectional study was carried out in Haematology / Pathology department, Army Medical College, National University of Medical Sciences (NUMS) in collaboration with Immunology and Haematology departments of Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January, 2019 to 31st December, 2019. Seventy-three (73) recently diagnosed patients of Acute Lymphoblastic leukaemia of all age groups and both genders were included in the study. A proforma was used to note demographic data. CBC, cytochemical stains and bone marrow examinations were carried out and assessed for morphology and percentage of blasts using a microscope. Flow cytometry was used to perform immunophenotyping on samples of peripheral blood and bone marrow, using a standard panel. RESULTS: The most commonly expressed markers were weak CD45, TdT, CD19, CD10 and HLA-DR. Weak CD45 was present in almost all blast cells and there was no remarkable difference in its positivity among various subtypes of ALL. Myeloid expression was observed in 13 (17.8%) cases. CD13 and CD33 were aberrantly expressed in 11 and 12.3 of all cases of ALL respectively. CONCLUSIONS: Expression of aberrant myeloid CD markers in acute lymphocytic leukaemia has prognostic significance and should be documented during lineage assignment of acute leukaemias while performing immunophenotyping.

Enhanced Gene Delivery and CRISPR/Cas9 Homology-Directed Repair in Serum by Minimally Succinylated Polyethylenimine.

Gene therapy aims to treat patients by altering or controlling gene expression. The field of gene therapy has had increasing success in recent years primarily using viral-based approaches; however, there is still significant interest toward the use of polymeric materials due to their potential as flexible, low-cost scaffolds for gene delivery that do not suffer the mutagenesis and immunogenicity concerns of viral vectors. To address the challenges of efficiency and biocompatibility, a series of zwitterion-like polyethylenimine derivatives (zPEIs) were produced via the succinylation of 2-11.5% of polyethylenimine (PEI) amines. With increasing modification, zPEI polyplexes exhibited decreased serum-protein aggregation and dissociated more easily in the presence of a competitor polyanion when compared to unmodified PEI. Surprisingly, the gene delivery mediated in the presence of serum showed that succinylation of as few as 2% of PEI amines resulted in transgene expression 260- to 480-fold higher than that of unmodified PEI and 50- to 65-fold higher than that of commercial PEI-PEG2k in HEK293 and HeLa cells, respectively. Remarkably, the same zPEIs also produced 16-fold greater efficiency of CRISPR/Cas9 gene knock-in compared to unmodified PEI in the presence of serum. In addition, we show that 2% succinylation does not significantly decrease polymer/DNA binding ability or serum protein interaction to a significant extent, yet this small modification is still sufficient to provide a remarkable increase in transgene expression and gene knock-in in the presence of serum.

Our experience of treating adult bone lymphoma, A retrospective cross-sectional study in a tertiary care center, Aga Khan University Hospital, Karachi.

OBJECTIVE: To determine the experience at the Aga Khan University Hospital in diagnosing and treating adult patients with primary lymphoma of bone. METHODOLOGY: All patients with Primary lymphoma of bone (PLB) that were diagnosed and/or treated at Aga Khan University Hospital, Karachi from 2005 to 2019 were included as part of this study. RESULTS: There were 17 patients with PLB including 13 (76.5%) males and 4 (23.5%) females with a mean age of 44 ± 16.5 years. Nine patients were between 30-59 years of age at diagnosis. The mean follow-up time of patients was 80±46.7 months. Six patients had tumours of pelvic bone followed by tibia (5) and femur (4). Four patients had a pathological fracture at the time of presentation whereas 2 (11.8%) required surgical fixation of the pathological fracture. The stage of the tumour was based on Ann Arbor classification. Nine (52.9%) cases had Stage 1 disease, 7 (41.2%) had stage IV disease with metastasis in extra nodal tissues. As for treatment, every patient received chemotherapy whereas 5 (29.4%) received adjuvant radiotherapy. Complete remission in the size of the tumour was seen in 11 (64.7%) patients while 6 (35.3%) had partial remission. Post-treatment, 4 (23.5%) patients expired. The mean Overall Survival (OS) time was 80.18 ± 46.71months with a survival rate of 76.5. CONCLUSIONS: Primary lymphoma of the bone can be treated with medical regime and good prophylactic surgeries to avoid pathological fracture such as intramedullary nailing.

Physiological Responses to Linear and Nonlinear Soccer-specific Match Simulations and Their Effects on Lower-Limb Muscle Fatigue.

Uddin, N, Jeffries, O, Read, P, Howe, L, Patterson, S, and Waldron, M. Physiological responses to linear and nonlinear soccer-specific match simulations and their effects on lower-limb muscle fatigue. J Strength Cond Res 34(11): 3232-3240, 2020-The aims of this study were to: (a) investigate the effects of linear and nonlinear soccer simulations on lower-limb muscle function and physiological responses and (b) evaluate the relationship between match-running demands and changes in lower-limb muscle function. In a repeated-measures cross-over design, 8 participants completed either a linear or nonlinear adapted Loughborough Intermittent Shuttle Test (LIST) on 2 occasions. The movement of players was tracked with a global positioning system, while lower-limb muscle function tests and physiological measurements were performed before and every 15 minutes during the simulation. There were no differences in distance covered, yet high-speed running (p = 0.007), accelerations (p = 0.008), and decelerations (p = 0.015) were higher in the linear LIST. Mean heart rate (p = 0.001) and ratings of perceived exertion (p = 0.013) were higher in the nonlinear LIST. Peak landing forces (p = 0.017) and jump height (p = 0.001) were reduced between baseline and 90 minutes but were not different between conditions. Changes in peak landing forces from baseline to half-time (r = -0.57, n = 16, p = 0.022) and full-time (r = -0.58, n = 16, p = 0.019) were related to high-speed running. Hamstring force was unaffected by time (p = 0.448) but was reduced in the linear LIST (p = 0.044). Protocols posing different external and internal demands elicited similar levels of fatigue across simulations. Hamstring function was not an effective indicator of fatigue, but our results highlight the greater demands placed on this muscle group when higher-speed running is performed.

A 10-year review of histopathological findings of enucleated eyes from a tertiary-care center, Pakistan.

OBJECTIVE: To determine the histopathology of enucleated eye specimens. METHODS: The 10-year inventory was conducted at Aga Khan University Hospital, Karachi, and comprised all histopathology reports of enucleated eye specimens received from January 2007 to December 2016 by the Section of Histopathology, Department of Pathology. SPSS 19 was used for data analysis. RESULTS: A total of 232 ocular tissue specimens from 231 patients were evaluated. Ocular tumours were the most common histopathological diagnosis 186(80%). Among tumours, retinoblastoma was the most common 137(59%) followed by malignant melanoma 31(13%) and squamous cell carcinoma 15(6.5%). Overall, 16(6.9%) specimens had degenerative changes secondary to different ocular disorders. Staphyloma and Coat's disease was diagnosed in 3(1.3%) cases each. In 4(1.7%) cases, there was no formal diagnosis. CONCLUSIONS: Early identification of tumours may allow for conservative management and limit the need for enucleations.

Prognostic markers in Chronic Lymphocytic Leukaemia - A flow cytometric analysis.

OBJECTIVE: To find out the frequency of ZAP-70, CD38 and CD49d in patients diagnosed with CLL in our population. METHODS: This is a cross sectional study conducted in Army Medical College in collaboration with Armed Forces Institute of Pathology and Military Hospital Rawalpindi from 1st January 2018 to 30th November 2018. Permission from Institutional Ethical Committee was obtained. Blood samples were collected by non-probability consecutive sampling technique and analyzed for blood counts and flow cytometry was done for ZAP-70, CD38 and CD49d. Manufacturer's instructions for the kits were strictly followed. RESULTS: Fifty-one newly diagnosed patients with CLL were studied for the prognostic markers in CLL. CD 38 was expressed in 25(49%) and CD49d in 21(41.2%). ZAP-70 expression was not detected in our series of patients. CONCLUSION: We conclude that CD38 and CD49d expression was detected in almost half of the patients of CLL in our series. CD49d showed statistically positive correlation with CD38, showing that it is a more pragmatic choice for reliable prognostication of CLL along with CD38.

Real-Time Interrogation of Aspirin Reactivity, Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy.

Hyperpolarized magnetic resonance spectroscopy enables quantitative, non-radioactive, real-time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single- and double-13 C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T1 ) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13 C-NMR spectroscopy. Hyperpolarized, double-labeled aspirin was well tolerated in mice and could be observed by both 13 C-MR imaging and 13 C-NMR spectroscopy in vivo.

Quantification of nanoparticle release from polymer nanocomposite coatings due to environmental stressing.

Certain engineered nanoparticles (ENP) reduce the flammability of components used in soft furnishings (mattresses and upholstered furniture). However, because of the ENP's small size and ability to interact with biological molecules, these fire retardant ENPs may pose a health and environmental risks, if they are released sometime during the life cycle of the soft furnishing. Quantifying the released amount of these ENPs under normal end-use circumstances provides a basis for assessing their potential health and environmental impact. In this article, we report on efforts to identify suitable methodologies for quantifying the release of carbon nanofibers, carbon nanotubes, and sodium montmorillonites from coatings applied to the surfaces of barrier fabric and polyurethane foam. The ENPs released in simulated chewing and mechanical stressing experiments were collected in aqueous solution and quantified using Ultraviolet-Visible and inductively coupled plasma-optical emission spectroscopy. The microstructures of the released ENPs were characterized using scanning electron microscopy. The reported methodology and results provide important milestones to estimate the impact and toxicity of the ENP release during the life cycle of the nanocomposites. To our knowledge, this is the first study of ENP release from the soft furnishing coating, something that can be important application area for fire safety.

Spindle cell/pleomorphic lipomas of the face: an under-recognized diagnosis.

AIMS: Rarely, spindle cell/pleomorphic lipomas arise on the face where they present diagnostic difficulties. The aim of our study was to describe the clinical, histological and immunohistochemical features of a series of spindle cell/pleomorphic lipomas of the face. METHODS AND RESULTS: Thirty-three cases of spindle cell/pleomorphic lipoma of the face were studied. Patient characteristics were 25 male:8 female, ranging from 33 to 91 years of age (mean 60). The most common sites were nose (nine), cheek (eight), forehead (eight), chin (three), anterior scalp (three), lip (two) and ear (two). The mean tumour size was 1.9 cm. An unusual histological feature was the involvement of skeletal muscle, which was seen in 12 cases (36%). Otherwise, the cases exemplified the entire histological spectrum of spindle cell lipoma, including purely dermal and subcutaneous cases. By immunohistochemistry, they were uniformly positive for CD34 (26 of 26 cases), positive for oestrogen receptor in five of 21 cases and negative for desmin in all cases (none of 20 positive). Retinoblastoma (Rb) expression was lost in 18 of 19 cases. CONCLUSIONS: Due to an unusual anatomical location and frequent infiltration of skeletal muscle, spindle cell/pleomorphic lipoma of the face can be a difficult diagnosis. Increased awareness of its clinicopathological features should allow accurate classification.

A wearable sensors dataset for stress & boredom associated activity recognition.

This article presents a dataset of activities associated with stress and boredom obtained through wearable sensors. Data was collected from 40 right-handed participants aged 20 to 25, evenly split between males and females. Each individual wore a smart device on their dominant arm's wrists to facilitate the capture of data. This dataset covers five activities associated with stress and boredom, namely, smoking, eating, nail biting, face touching, and staying still. These activities were selected for their potential psychological implications and captured in an uncontrolled environment to mimic real-life scenarios. The data provides a unique resource for developing machine learning models aimed at recognizing these behaviors, which could lead to real-time analysis and interventions for stress. A custom holder was used to hold the device on the wrists in order to ensure that all participants had consistent orientation and placement. This holder was situated just above the wrist joint, a location typically associated with the placement of smartwatches. The dataset provides a unique opportunity for developing machine learning models for stress & boredom associated activities recognition apart from real-time symptomatic analysis of stress and boredom.

StresSense: Real-Time detection of stress-displaying behaviors.

BACKGROUND: Wrist-worn gadgets like smartphones are ideal for unobtrusively gathering user data, in various fields such as health and fitness monitoring, communication, and productivity enhancement. They seamlessly integrate into users' daily lives, providing valuable insights and features without the need for constant attention or disruption. In sensitive domains like mental health, these devices provide user-friendly, privacy-protected means of diagnosis and treatment, offering a secure and cost-effective avenue for seeking help. OBJECTIVES: This study addresses the limitations of traditional mental health assessment techniques, such as intrusive sensing and subjective self-reporting, by harnessing the unobtrusive data collection capabilities of smartphones. Equipped with accelerometers and other sensors, these devices offer a novel approach to mental health research. Our objective was to develop methods for real-time detection of stress and boredom behavior markers using smart devices and machine learning algorithms. METHODOLOGY: By leveraging data from accelerometers (A), gyroscopes (G), and magnetometers (M), we compiled a dataset indicative of stress-related behaviors and trained various machine-learning models for predictive accuracy. The methodology involved collecting data from motion sensors (A, G, and M) on the dominant arm's wrist-worn smartphone, followed by data preprocessing, transformation from time series format, and training a Deep Neural Network (DNN) model for activity recognition. FINDINGS: Remarkably, the DNN achieved an accuracy of 93.50% on test data, outperforming traditional and ensemble machine learning methods across different window sizes, and demonstrated real-time accuracy of 77.78%, validating its practical application. CONCLUSION: In conclusion, this research presents a novel dataset for detecting stress and boredom behaviors using smartphones, reducing reliance on costly devices and offering a more objective assessment. It also proposes a DNN-based method for wrist-worn devices to accurately identify complex activities associated with stress and boredom, with benefits in terms of privacy and user convenience. This advancement represents a significant contribution to the field of mental health research, providing a less intrusive and more user-friendly approach to monitoring mental well-being.

Solitary Skull Langerhans Cell Histiocytosis Presenting With a Pus Draining Fistula: An Unusual Presentation and Review of Literature.

Langerhans cell histiocytosis (LCH) is a rare condition in adults, especially when it is limited to a single area of the skull, known as solitary calvarial involvement. In this case report, we present a unique instance of LCH affecting the parietal bone with a pus-draining fistula. This is a rare and unusual presentation at this location, which has been scarcely reported in medical literature. A 30-year-old woman with no prior comorbidity presented with complaints of headache that persisted for a year. She also had swelling on her scalp and a yellowish discharge for 3 weeks, but no neurological problems were observed. Radiology revealed thinning of the calvaria, with ragged margins along the inner table, multiple focal erosions, and involvement of overlying soft tissue and bony sequestrum. The patient underwent biparietal craniotomy and excision of the lesion. The histopathology report showed LCH. After 8 months of follow-up, there was no recurrence. The management of solitary calvarial involvement by LCH with masquerading presentation as a scalp infection can be achieved through complete excision of the lesions, resulting in a favorable outcome.

Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome.

Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.

Anaplerotic nutrient stress drives synergy of angiogenesis inhibitors with therapeutics targeting tumor metabolism.

Tumor angiogenesis is a cancer hallmark, and its therapeutic inhibition has provided meaningful, albeit limited, clinical benefit. While anti-angiogenesis inhibitors deprive the tumor of oxygen and essential nutrients, cancer cells activate metabolic adaptations to diminish therapeutic response. Despite these adaptations, angiogenesis inhibition incurs extensive metabolic stress, prompting us to consider such metabolic stress as an induced vulnerability to therapies targeting cancer metabolism. Metabolomic profiling of angiogenesis-inhibited intracranial xenografts showed universal decrease in tricarboxylic acid cycle intermediates, corroborating a state of anaplerotic nutrient deficit or stress. Accordingly, we show strong synergy between angiogenesis inhibitors (Avastin, Tivozanib) and inhibitors of glycolysis or oxidative phosphorylation through exacerbation of anaplerotic nutrient stress in intracranial orthotopic xenografted gliomas. Our findings were recapitulated in GBM xenografts that do not have genetically predisposed metabolic vulnerabilities at baseline. Thus, our findings cement the central importance of the tricarboxylic acid cycle as the nexus of metabolic vulnerabilities and suggest clinical path hypothesis combining angiogenesis inhibitors with pharmacological cancer interventions targeting tumor metabolism for GBM tumors.